Safety of Boron Neutron Capture Therapy with Borofalan(10B) and Its Efficacy on Recurrent Head and Neck Cancer: Real-World Outcomes from Nationwide Post-Marketing Surveillance.

BACKGROUND: This study was conducted to evaluate the real-world safety and efficacy of boron neutron capture therapy (BNCT) with borofalan(10B) in Japanese patients with locally advanced or locally recurrent head and neck cancer (LA/LR-HNC). METHODS: This prospective, multicenter observational study was initiated in Japan in May 2020 and enrolled all patients who received borofalan(10B) as directed by regulatory authorities. Patient enrollment continued until at least 150 patients were enrolled, and adverse events attributable to drugs, treatment devices, and BNCT were evaluated. The patients with LA/LR-HNC were systematically evaluated to determine efficacy. RESULTS: The 162 patients enrolled included 144 patients with squamous cell carcinoma of the head and neck (SCCHN), 17 patients with non-SCCHN (NSCCHN), and one patient with glioblastoma. Treatment-related adverse events (TRAEs) were hyperamylasemia (84.0%), stomatitis (51.2%), sialoadenitis (50.6%), and alopecia (49.4%) as acute TRAEs, and dysphagia (4.5%), thirst (2.6%), and skin disorder (1.9%) as more common late TRAEs. In patients with LA/LR-HNC, the overall response rate (ORR) was 72.3%, with a complete response (CR) in 63 (46.0%) of 137 patients with SCCHN. Among 17 NSCCHN patients, the ORR was 64.7%, with eight cases (47.1%) of CR. One- and two-year OS rates in patients with recurrent SCCHN were 78.8% and 60.7%, respectively. CONCLUSIONS: This post-marketing surveillance confirmed the safety and efficacy of BNCT with borofalan(10B) in patients with LA/LR-HNC in a real-world setting.

The Wait Time for Surgery Following Injury Affects Functional Outcomes and Complications After an Ankle Fracture: A Propensity Score-Matched Multicenter Study, the TRON Study.

BACKGROUND: The present study aimed to evaluate the hypothesis that a 1-week extension of the waiting period to perform surgery for ankle fracture might affect postoperative results and complications. METHODS: We used our multicenter database named TRON (Trauma Research Group of Nagoya). In all, 779 patients who underwent surgery for ankle fracture, who had no comorbidities were eligible. After exclusion, we analyzed 596 patients. We divided the patients into 2 groups according to whether they were operated on within 7 days after the injury with propensity score matching. RESULTS: The operative time of the delayed operation group (DO group) was significantly longer than that of the early operation group (EO group) (115.87 ± 56.59 vs 85.93 ± 34.58 minutes; P < .001). The rate of infection in the DO group was significantly higher than that of the EO group (16 patients [6.5%] vs 4 patients [1.6%]; P = .016). CONCLUSION: Waiting for more than a week to perform ankle surgery may lead to longer operative times and increased infection rates. LEVELS OF EVIDENCE: III.

Early weight bearing and mobilization decrease perioperative complications in patients after ankle fracture; the retrospective multicenter (TRON group) study.

BACKGROUND: Open reduction and internal fixation (ORIF) for unstable ankle fractures (AF) are relatively predictable with excellent outcomes. Rehabilitation strategies are still being debated after surgical intervention for AF: non-weight bearing and cast immobilization for six weeks after the surgical repair of unstable AF or early functional treatment with partial weight bearing. This study aimed to compare early weight bearing and functional outcomes and complications. METHODS: Between April 2014 and March 2019, 1421 patients with AF underwent ORIF at 11 institutions (TRON group). The patients were divided into two groups: Group E started weight bearing within six weeks after surgery, and group L started weightbearing for more than six weeks after. To adjust for baseline difference between groups, a propensity score-matched algorithm was used to match Group E with Group L in a 1:1 ratio of 294 cases each. We compared the American Orthopedic Foot and Ankle Society (AOFAS) score as the functional outcome, the rate of wound dehiscence, superficial and deep infections, blistering, nonunion, neurapraxia, and reoperation at 3, 6, and 12 months after surgery. RESULTS: The mean period of non-weight bearing was significantly shorter in group E (3.68 ± 1.02 vs. 6.67 ± 1.43; P < 0.001). The mean period of cast immobilization term were shorter in group E (1.84 ± 1.35 vs. 2.65 ± 1.51; P < 0.001). There were no differences in the AOFAS score at any period. The rates of deep infection and reoperation in Group E were significantly lower than those in Group L (1.7% vs. 6.1%; P = 0.009, 2.0% vs. 7.8%; P = 0.002, respectively). There were no significant differences in superficial infection (9 vs. 15; P = 0.297), nonunion (9 vs. 15 P = 0.30), blistering (4 vs. 3; P = 1.00), neurapraxia (2 vs. 1; P = 1.00), and wound dehiscence (15 vs. 18; P = 0.72). CONCLUSIONS: Although functional outcome was similar depending on whether early weight bearing was allowed, the rates of deep infection and reoperation decreased in patients with early weight bearing. We recommend early postoperative weight bearing in patients with a surgically treated AF.

Smoking and trimalleolar fractures are risk factors for infection after open reduction and internal fixation of closed ankle fractures: A multicenter retrospective study of 1,201 fractures.

INTRODUCTION: One of the complications of the surgical therapy for ankle fractures includes wound infection. This study aimed to evaluate postoperative function and clarify the risk factors associated with postoperative wound infection in patients receiving the open reduction and internal fixation for ankle fracture through a multicenter study. SUBJECTS AND METHOD: Among 1421 patients diagnosed as having closed ankle fracture and who were treated by surgical therapy in 11 institutions from 2014 through 2019, 1201 patients (men, n = 512, women, n = 689; the mean (SD) age, 50.9 (15.6) years; the mean body mass index [BMI] (SD), 24.3 (4.2) kg/m2) were included as subjects. Excluded were 220 patients due to self-termination of treatment, inability to follow up after discharge, open fracture, distal tibia shaft fracture, and pilon fracture. We extracted the following as risk factors of wound infection: age, sex, BMI, fracture type, injury energy and histories of smoking, diabetes, arteriosclerosis, heart failure and myocardial infarction. We conducted logistic regression analysis to investigate the risk factors of wound infection using these extracted items as explanatory variables and the presence or absence of wound infection as the response variable. RESULTS: Wound infection occurred after surgery for closed ankle fracture in 69 the 1201 patients (5.7%). The causative organism was methicillin-susceptible Staphylococcus aureus (MSSA) in 15 patients, methicillin-resistant S. aureus (MRSA) in 4 patients, Finegoldia magna in one patient, and S. haemolyticus in one patient. In the other patients, causative organisms were not detected, culture of the causative organisms was not conducted, or they were unknown. The univariate analysis showed significant differences in sex (p = 0.01) and for smoking (p = 0.002), fracture type (p = 0.02) and heart failure (p = 0.042). Logistic regression analysis showed that smoking and type of fracture (trimalleolar fracture) were significant explanatory factors for infection (odds ratio 1.83 and 1.98, p = 0 .040 and 0.042, respectively). CONCLUSIONS: At 5.7%, the rate of postoperative wound infection in closed ankle fracture was not low. Staphylococcus was the most frequent causative organism. The surgeon should pay attention infection after surgery in the patients who had a trimalleolar fracture or smoking habits.

Who Needs Longer Tolvaptan Treatment?

The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been approved for heart failure patients with volume overload in Japan. In this study (SMILE study), we investigated patient characteristics and effectiveness in both a 14 days and shorter treated group (14DS) and 15 days and longer treated group (15DL). The results showed that the patients in the 15DL group had low cardiac output with intensive diuretic administration (ie, diuretic resistance). The congestive symptoms were greatly improved within 14 days of treatment in both the 14DS and 15DL groups. Further improvements in lower limb edema, pulmonary congestion, dyspnea, third sound, and rales after 2 weeks were statistically significant in the 15DL group, but the amount of improvement was subtle and the 15DL group might have consisted of a considerable number of "non-responders". Therefore, identifying "responders" by biomarkers and conducting a prospective randomized study is required to validate our findings.

Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

AIM: Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. METHODS: Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. RESULTS: Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%). CONCLUSIONS: In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained.

Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study).

The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been found to improve symptoms in patients with congestive heart failure. In this study (SMILE study), we administered tolvaptan to patients aged ≥ 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients < 80 years (U-80). The results showed that the effectiveness of tolvaptan in the aged patients was similar to that in U-80 patients. In the safety profile, the incidence rate of thirst was lower in the aged patients than that in U-80 patients (9.6% versus 11.6%, P = 0.0023). Furthermore, the incidence of hypernatremia, defined as ≥ 150 mEq/L in aged patients, was comparable with that in U-80 patients (2.9% versus 3.6%, respectively, P = 0.3657). Based on these findings, tolvaptan has similar effectiveness and safety profiles in aged patients compared with U-80 patients. In addition, we found that a higher starting dose of tolvaptan was markedly associated with the occurrence of hypernatremia exclusively in the aged population; therefore, we recommend that tolvaptan should be started at lower doses in aged patients.